Antibiotics, not dirty hospitals, the main cause of C. difficile epidemic

The study concluded that overuse of antibiotics like ciprofloxacin led to the outbreak of severe diarrhoea caused by C. difficile that hit headlines from 2006 onwards. The outbreak was stopped by substantially reducing use of ciprofloxacin and related antibiotics.

Inappropriate use and widespread over prescribing of fluoroquinolone antibiotics such as ciprofloxacin in fact allowed C. difficile bugs that were resistant to the drug to thrive, because non-resistant bugs in the gut were killed off by the antibiotic, leaving the way clear for rapid growth of resistant C. difficile.

Concerns about hospital "superbugs" which had become resistant to common antibiotics resulted in the announcement of a programme of "deep cleaning" and other infection control measures in the NHS in 2007.

The study, by the University of Oxford, University of Leeds and Public Health England and published today in The Lancet Infectious Diseases, found that cases of C. difficile fell only when fluoroquinolone use was restricted and used in a more targeted way as one part of many efforts to control the outbreak.

The restriction of fluoroquinolones resulted in the disappearance in the vast majority of cases of the infections caused by the antibiotic-resistant C. difficile, leading to around an 80% fall in the number of these infections in the UK (in Oxfordshire approximately 67% of C. difficile bugs were antibiotic-resistant in September 2006, compared to only approximately 3% in February 2013).

In contrast, the smaller number of cases caused by C. difficile bugs that were not resistant to fluoroquinolone antibiotics stayed the same. Incidence of these non-resistant bugs did not increase due to patients being given the antibiotic, and so were not affected when it was restricted.

At the same time, the number of bugs that were transmitted between people in hospitals did not change. This was despite the implementation of comprehensive infection prevention and control measures, like better handwashing and hospital cleaning in this case.

The study's authors therefore conclude that ensuring antibiotics are used appropriately is the most important way to control the C. difficile superbug. The authors note that it is important that good hand hygiene and infection control continues to be practiced to control the spread of other infections.

The study, analysed data on the numbers of C. diff infections and amounts of antibiotics used in hospitals and by GPs in the UK.

More than 4,000 C. diff bugs also underwent genetic analysis using a technique called whole genome sequencing, to work out which antibiotics each bug was resistant to.

Co-author Derrick Crook, Professor of Microbiology, University of Oxford said: "Alarming increases in UK hospital infections and fatalities caused by C. difficile made headline news during the mid-2000s and led to accusations of serious failings in infection control.

"Emergency measures such as 'deep cleaning' and careful antibiotic prescribing were introduced and numbers of C. difficile infections gradually fell by 80% but no-one was sure precisely why.

"Our study shows that the C. difficile epidemic was an unintended consequence of intensive use of an antibiotic class, fluoroquinolones, and control was achieved by specifically reducing use of this antibiotic class, because only the C. difficile bugs that were resistant to fluoroquinolones went away.

"Reducing the type of antibiotics like ciprofloxacin was, therefore, the best way of stopping this national epidemic of

C. difficile and routine, expensive deep cleaning was unnecessary. However it is important that good hand hygiene continues to be practiced to control the spread of other infections.

"These findings are of international importance because other regions such as North America, where fluoroquinolone prescribing remains unrestricted, still suffer from epidemic numbers of C. difficile infections."
Co-author Prof Mark Wilcox, Professor of Microbiology, University of Leeds, said: "Our results mean that we now understand much more about what really drove the UK epidemic of C. diff infection in the mid-2000s.

"Crucially, part of the reason why some C. diff strains cause so many infections is because they find a way to exploit modern medical practice.

Similar C. diff bugs that affected the UK have spread around the world, and so it is plausible that targeted antibiotic control could help achieve large reductions in C. diff infections in other countries."

The funding for the study came from the UK Clinical Research Collaboration, (Medical Research Council, Wellcome Trust, National Institute for Health Research); NIHR Oxford Biomedical Research Centre; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antibiotic Resistance, University of Oxford in partnership with Leeds University and Public Health England; NIHR Health Protection Research Unit in Modelling Methodology, Imperial College London in partnership with Public Health England; and the Health Innovation Challenge Fund.

Clostridium difficile is a bacterium that can infect the bowel and cause diarrhoea.

The infection most commonly affects people who have recently been treated with antibiotics, but can spread easily to others.

In some cases, serious complications can develop, such as damage to the bowel or severe dehydration, which may cause drowsiness, confusion, a rapid heart rate and death.

Oxford University Hospitals NHS Foundation Trust (OUH) is one of the largest acute teaching trusts in the UK, with a national and international reputation for the excellence of its services and its role in patient care, teaching and research. The Trust supports world-leading research programmes in cardiovascular diseases, musculoskeletal disorders, neurological disorders such as Parkinson's and Alzheimer's through its designation as one of the UK's five comprehensive biomedical centres and units. It works in close partnership with the University of Oxford and is a leading centre for cancer, neurosciences, diabetes, genetics and many other fields. Research themes of particular strength are: cancer, cardiovascular science, diabetes, endocrinology & metabolism, infection and immunology, musculoskeletal science, neuroscience and reproduction and development. As of October 1 2015, the Trust was awarded Foundation Trust status. This decision comes after the Care Quality Commission gave OUH an overall rating of 'Good' in May 2014, and after scrutiny of the Trust's quality, finances, service delivery and governance arrangements by the NHS Trust Development Authority and Monitor. The Trust has been designated as a major trauma centre and is one of four UK centres for craniofacial surgery and The Trust employs over 12,000 staff and consists of four hospitals: the Churchill Hospital, John Radcliffe Hospital and Nuffield Orthopaedic Centre in Oxford and the Horton General Hospital in Banbury. http://www.ouh.nhs.uk

The University of Oxford's Medical Sciences Division is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students. The University is rated the best in the world for medicine, and it is home to the UK's top-ranked medical school. From the genetic and molecular basis of disease to the latest advances in neuroscience, Oxford is at the forefront of medical research. It has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic. Partnerships with the local NHS Trusts enable patients to benefit from close links between medical research and healthcare delivery. A great strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions.

The NIHR Oxford Biomedical Research Centre is funded by the National Institute for Health Research, and is a partnership between the Oxford University Hospitals NHS Foundation Trust and the University of Oxford. The NIHR provides the NHS with the support and infrastructure it needs to conduct first-class research funded by the Government and its partners alongside high-quality patient care, education and training. Its aim is to support outstanding individuals (both leaders and collaborators), working in world class facilities (both NHS and university), and conducting leading edge research focused on the needs of patients.

The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. The NIHR is the research arm of the NHS. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government's strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website.

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